1. Field of the Invention
The present invention relates to MDC proteins, DNAs encoding the same, and gene analysis methods using the DNAs. The present invention can be utilized in such fields as medical treatment and diagnosis.
2. Description of the Related Art
The opinion that mutations in cellular proteins play an important role in the onset of cancer has been known for long. Recent advancement in genetic engineering enables analysis of gene mutations in tumor cells, and has brought about a marked progress in the field of cancer research.
Up to this time, the analysis and identification of oncogenes have made such progress that the number thereof has amounted to several tens. On the other hand, attention has been focused on tumor suppressor genes for these several years. The tumor suppressor genes which have been discovered thus far include the Rb gene for retinoblastoma (Friend, S. H. et al., Proc. Natl. Acad. Sci. USA, 84, 9095, 1987), the p53 gene (Lane, D. P. et al., Nature, 278, 261, 1979) and the APC gene (Kenneth, W. K. et al., Science, 253, 661, 991) for colorectal tumor, the WT1 gene for Wilms' tumor (Call, K. M. et al., Cell, 60, 509, 1990), and the like. In the case of the p53 gene, some families are known to be inheriting mutations in the gene ["Li-Fraumeni syndrome" (Makin, D. et al., Science, 250, 1233, 1990; Srivastava, S. et al., Nature, 348, 747, 1990)]. Moreover, it is becoming increasingly clear that defects in multiple genes, and not in a single gene, contribute to the progression of the malignant phenotype of cancer, and it is believed that there exist much more unidentified oncogenes and tumor suppressor genes. The discovery and elucidation of them are expected by not only investigators and clinicians, but also common people in all the world.
Breast cancer is classified into hereditary (familial) breast cancer and nonhereditary (sporadic) breast cancer, and hereditary breast cancer is classified into early-onset and late-onset diseases according to the age of onset. It has been revealed by linkage analyses that, at least early-onset familial, breast cancer linked to a very small region on chromosome 17 (Hall, J. M. et al., Science, 250, 1684-1689, 1990). Moreover, it has been shown that hereditary ovarian cancer is also linked to the same region (Narod, S. A. et al., Lancet, 338, 82-83, 1991).
Accordingly, it is believed that a tumor suppressor gene is present in this region and protein deficiency or mutation induced by an allelic deletion or mutation of the gene is one of the causes of breast and ovarian cancers.
It is believed that in the onset of common (sporadic) breast cancer as well, the occurence of an acquired mutation or allelic deletion of the gene in this region results in protein mutation or deficiency and this causes the transformation of a normal cell to a breast cancer (Sato et al., Cancer Res., 51, 5794-5799, 1991). Consequently, isolation of the causative gene present in this region and identification of the protein encoded by the gene are expected as an urgent problem to not only physicians and investigators in all the world, but also common people, particularly women in Europe and America where there are numerous patients with breast cancer.
The present invention provides novel proteins involved in breast and ovarian cancers, DNAs encoding them, and methods for the testing and diagnosis of cancer by using them.
The present inventors disclose a novel gene encoding a 524-amino acid protein which was isolated from chromosomal region 17q21.3 where a tumor suppressor gene(s) for breast and ovarian cancers is thought to be present (Nature genetics, 5, 151-157, 1993; this paper is refered in Nature genetics, 5, No. 2, 101-102, 1993).